The immune response is a highly regulated process with deficient activation being manifested by decreased resistance to infectious illness and possibly malignancy and altered, poorly controlled activation by allergy and autoimmunity. Triggering and much of the modulation of the inflammatory and/or immune responses appear to be exerted through specific receptors for antigens, immunoglobulins and complement. The research proposed here will combine the principal investigator's prior training in complement and immunopharmacology in order to explore the function of these receptors on highly purified immunocompetent cells in regard to their susceptibility to pharmacologic modulation, mode of biochemical linkage to the interior of the cell, kinetics of binding and physiochemical properties. Phagocytosable particles will be sensitized with immunoglobulins and/or complement and then granulocytes and moncytes challenged with these stimuli. The alteration of cellular metabolism consequent to the attachment and/or ingestion will be examined in regards to cyclic nucleotide concentration, protein phosphorylation and cytochalasin binding proteins. In related studies ascorbic acid and ethanol, agents which alter cyclic nucleotide levels, will be examined as to their ability to modulate mitogenesis, histamine release and lysosomal enzyme release. Utilizing affinity chromatography and immunoprecipition, isolation and characterization of the C3b receptor on immunocompetent cells will be pursued. The key objective of these investigations is to obtain a better understanding of the mechanisms whereby surface phenomena, consisting of the attachment and in some cases, membrane bound complexes, occur and then mediate and/or modulate appropriate cellular response.